Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism?

Abstract

Betaine homocysteine methyltransferase (BHMT), a Zn(2+)-dependent thiolmethyltransferase, contributes to the regulation of homocysteine levels, increases in which are considered a risk factor for cardiovascular diseases. Most plasma homocysteine is generated through the liver methionine cycle, in which BHMT metabolizes approximately 25% of this non-protein amino acid. This process allows recovery of one of the three methylation equivalents used in phosphatidylcholine synthesis through transmethylation, a major homocysteine-producing pathway. Although BHMT has been known for over 40 years, the difficulties encountered in its isolation precluded detailed studies until very recently. Thus, the last 10 years, since the sequence became available, have yielded extensive structural and functional data. Moreover, recent findings offer clues for potential new functions for BHMT. The purpose of this review is to provide an integrated view of the knowledge available on BHMT, and to analyze its putative roles in other processes through interactions uncover to date.

Mouse Betaine-Homocysteine S-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue

“…BHMT is one of the most abundant proteins in the liver, representing 0.6 -1.6% of the total protein (24). However, its known functions are limited to its roles in choline and onecarbon metabolism.…”

Maternal dietary protein restriction and excess affects offspring gene expression and methylation of non-SMC subunits of condensin I in liver and skeletal muscle

“…31 Additionally, hepatic BHMT transcript amount was significantly increased in HP and LP pigs at dpn188, suggesting an increased availability of its substrate homocysteine, since BHMT metabolizes about 1/4 of homocysteine in the liver. 32 Accordingly, it is known that both methionine deficiency 33 and excess 34 increase BHMT activity by alteration of its gene expression. Therefore, the increased hepatic BHMT expression at dpn188 in LP and HP offspring is consistent with the increased MAT2B expression that can lead to higher homocysteine levels.…”

Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome

“…The former is a protein that remethylates Hcy to methionine using betaine as the methyl donor [29], and the latter is a protein known to catalyze the conversion of THF to the corresponding 10-formyl, 5,10-methenyl and 5,10-methylene derivatives [30] (Fig. 1).…”